.DESCRIPTION (provided by applicant): Pavlovian fear conditioning in rats is a powerful model system currently being used to study memory at the molecular, cellular, and systems level. Recent work with this procedure indicates that the formation of long-term memory for fear conditioning requires the synthesis of new mRNA and protein in the amygdala and hippocampus. Furthermore, it appears that after these memories are retrieved from storage they go through a second time period during which protein synthesis is required. Our data indicate that while initial learning requires both mRNA and protein synthesis in amygdala neurons, the "stabilization" of memory after retrieval does not require mRNA transcription. This suggests that while initial memory formation requires nuclear transcription, the modification of synapses after retrieval may involve dendridic protein synthesis using local mRNA. We also provide evidence showing that mRNA and/or protein synthesis is required for new learning not only in the amygdala, but also in structures throughout the neural circuit active during fear conditioning. The experiments proposed here will evaluate the relative contribution of mRNA transcription and protein translation to memory consolidation and "reconsolidation" at multiple brain sites including the amygdala, hippocampus, medial geniculate nucleus of the thalamus, and periaqueductal gray region of the midbrain. We will describe the relative post-training time course of these processes at several sites and begin to explore specific functional contributions of each brain area to learning. The results will provide important new insights into the mechanisms of memory formation and long-term stability at the molecular and systems level.